The proposed studies will define the various molecular forms of human and murine type I and type II interferons in terms of the extent of physicochemical and biologically detectable variations. By correlating these variations with their abilities to exert diverse antiviral, antitumor and non-antiviral activities in homologous and heterologous cells, we proposed to define structure-function relationships of the interferons. By isolation of interferon messenger RNAs from the various induced cells producing distinguishable human interferons or distinguishable mouse interferons and by translating these mRNAs in various cellular and cell-free systems under conditions either promoting or restricting posttranslational modifications, we propose to isolate modified interferons whose physicochemical and biological (antiviral : non-antiviral activity ratios and host-specificities) properties can be compared to native interferons, potentially enabling production of interferons with selected properties. We propose also to chemically or enzymatically degrade native or modified interferons to produce small "active-core" fragments which can themselves be characterized, to detect differences from native interferons in terms of physicochemical and biological properties. Studies on the affinities of the distinct forms of native interferons and of modified or fragmented interferons for various tissues are proposed to determine the physiological significance of distinct interferon forms.